Blood & Lymph System Exam 1

reduces FREE RADICALS to WATER

dehydration (diuretics, ethanol, excessive perspiration)

hypoxemia (certiain hemoglobinopathies which increase Hb affinity to O2; high altitude; pulmonary dz; kidney dz (artery stenosis); neoplastic conditions)

Production x survival = RBC mass

if survival is decreased (anemia of some sort)...production can increase up to 10x!

CBC
Reticulocyte Count
Blood Smear Exam

Erythrocyte count
Hematocrit
Hemoglobin concentration
RBC Indices (MCH/MCV/MCHC)
Peripheral smear review

Hematocrit
Hemoglobin concentration

MCV (mean corpuscular volume)

MCHC (mean corpuscular hemoglobin concentration)

RDW (red cell distribution width)

HIGH - huge variation in cell size - ANEMIA e.g. Iron deficiency anemia

LOW/NORMAL - all cells are about the same size (HEREDITARY problem - e.g. Thalassemia)

nonspecific variation in red cell SHAPE

nonspecific variation in red cell SIZE

oval: underying DNA defect

round: liver dz or alcoholism

Acanthocytes

ADVANCED LIVER DZ:
- neonatal hepatitis
- metastatic dz
- alcoholism

acanthocytes

echinocytes

echinocytes

Microangiopathic hemolytic anemia ******
DIC
TTP
HUS

Uremia
Malignant HTN
Severe Burns

artifact of staining
RBC's with inclusions
Abnormal vasculature/fibrosis/malignancies!

Immune hemolytic anemia ******
Microangiopathic hemolytic anemia
Thermal injury

target cells

Hemoglobinopathies (HbC, HbE, Thalassemia's, etc)

Reticulocytes - LARGER & more BLUE than normal due to INCREASED RNA content (polychromatophilic)

HEMOLYTIC ANEMIA's!

% observed reticulocytes x (Pt's Hct/45)

the degree of EFFECTIVE bone marrow compensation for anemia

used for evaluating bone marrow compensation for anemia & RESPONSE TO THERAPY!

HIGH IRF = adequate BM response or sign of successful therapy/graft
Normal/LOW IRF = inadequate BM response

IRF (immature reticulocyte fraction)

accumulation of ribosomal RNA due to incomplete degradation or abnormality in the RNA

- causes impaired Hb synthesis

Howell-Jolly Body (the little blue pieces are pieces of old DNA that's stuck in the cell...NOT iron!)

Pappenheimer body

Howell-Jolly Body = iron negative

Pappenheimer Body = iron positive

lead poisoning

Cabot Rings are seen with lead poisoning = a RING around the RBC!

RBC's clumping together in coin-like fashion

Multiple Myeloma; lymphoma

FALSLY elevates it.....RBC's clump & look like one giant MCV with a lot of volume

Cytometric (Morphological) classification

HI ACE

anemia of acute Hemorrhage
Immune hemolytic anemia

Aplastic anemia
anemias of Chronic disease
End organ failure (renal, endocrinopathy = decreased EPO!)

TIC(l)

Thalassemia **
Iron deficiency anemia **
anemia of chronic dz (LONG standing = infrequent)

LVR ('liver')

Liver dz
Vitamin B12/Folate deficiency***
Refractory anemias/Myelodyspastic syndrome

macrocytic

oval macrocytosis; DNA dysfunction****

round macrocyctosis; Alcoholism*** & Liver dz******

RBC's only - non-megaloblastic anemia

RBC/WBC/platelets - megaloblastic anemia

Both can be seen in megaloblastic anemia:
Hypersegmented PMN's - B12/Folate deficiency

Hyposegmented PMN's - Myelodyspastic syndrome

Auto Ab production
hyperglobulinemia
cold agglutinins
Increased reticulocyte counts (larger cells)
Extreme leukocytosis (larger cells)

Megaloblastic anemia (DNA dysfunction in cells)

B12 DEFICIENCY leading to megaloblastic anemia

oval macrocytes
Howell-Jolly bodies
hypersegmented neutrophils

THF (tetrahydrofolate)

vital in the metabolism of nucleotides & amino acids

deficiency causes a block in the conversion of dUMP to dTMP = defective DNA synthesis!

folic acid = 3-6 months

B12 - 2-6 years

hypersegmented neutrophils = will see before anemia..which comes a few weeks later! (will lead to megaloblastic anemia!)

homocysteine accumulation (can't convert to methionine)
folate deficiency

BOTH of which will cause decreased DNA synthesis

B12 (B12 has a 2-6yr supply whereas there is a 3-6 mo supply of folate)

B12 release from foods = b12 deficiency = megaloblastic anemia (B12 needs gastric acid to free it)

Intrinsic Factor (IF)

gastric atrophy! (Auto-Ab against parietal cells!)

INCREASE (can't excrete gastrin into the GI, so increases in serum)

Schilling test

Total homocystein (elevated in B12 & folate deficiencies)

Methylmalonic acid (elevated in B12 deficiency)

iron deficiency = hypo/micro anemia

thalassemia = hypo/micro anemia

Decreases heme synthesis (IDA)

Decreases globin synthesis (thalassemia)

blood loss

Iron deficiency anemia

Ferritin - won't stain (water soluble = washes away with stain)

Hemosiderin - will stain (water insoluble)

increases to suck up any available iron it can find

reduces all ferric iron (+3) to ferrous iron (+2)...which is the only form that can get absorbed in the duodenum

B12
Iron

1) decrease serum ferritin
2) increase transferrin
3) decrease serum iron
4) initial Normochromic/normocytic anemia...followed by classic hypochromic/microcytic anemia

low transferrin saturation by iron (ie. <30% = IDA!)

increased in IDA
decreased in ACD

decreased serum ferritin

serum ferritin is an ACUTE PHASE REACTANT, meaning that it's levels will be elevated in an inflammation or autoimmune dz = falsely elevated!

decreased in IDA
increased in ACD (iron overload!)

FEP is a precursor to heme, and if there is iron deficiency (IDA) OR a condition which blocks iron utilization (CDA), excess protoporphyrin that was destined to be converted to heme accumulates as FEP

Increased - IDA, ACD, lead poisoning

NORMAL - THALASSEMIA (defect in the number of normal globin synthesis...so heme binds iron fine)

block in the incorporation of iron into the protoporphyrin ring to form heme = abnormality of mitochondrial iron metabolism

Sideroblastic Anemia (can't hook up iron + protoporphyrin to make heme)

Anemia of Chronic Dz (defective iron reutilization)

BOTH cause the end result of lack of iron for Hb synthesis

Increased....this is a defect in hooking up iron with heme = can't make Hb...so iron deposits in the periphery of RBC = sideroblasts

acute myelogenous LEUKEMIA! because it's a STEM CELL DISORDER!

Alcohol
Lead (remember that microcytic hypochromic anemia is NOT characteristic of elevated lead levels in children..so can't use this to dx lead poisoning!! - most likely cause of micro/hypo anemia is IDA!)

Lead toxicity = low I, impaired development, mental concentration disorders)

normal physiologic immune response to protect the host from bugs &/or tumor cells...release of CYTOKINES result in iron deprivation, and inhibitor cytokines decrease erythropoiesis

cytokines are released due to CHRONIC inflammation = RA, SLE, Chron's, etc!
they're also released due to CHRONIC infections

cytokines shunt iron into macrophages and decrease macrophage release of iron = impaired iron recycling!
Also inhibit erythroid progenitor cell proliferation
Also decrease RBC survival time

HIV-1
parvovirus
Hep C

Diabetes
HYPOthyroidism (mild; don't need tx)

MACROCYTIC

these changes are often masked by concurrent RBC abnormalities from IRON deficiency...so the macrocytic cells shrink & look like normal cells

Jaundice (due to increased bilirubin)
Gallstones (due to increased bilirubin)
Dark red urine (due to intravascular hemolysis)

Acute hemolysis

Bone marrow hyperplasia
- thickened bone
- thin cortex

hemolytic crisis - viral infection = macrophages activated

Aplastic crisis - parvovirus B19 or Hep C causing impairement/cessation of BM red cell production

Marrow Exhaustion - depletion of nutrients, folic acid, or iron

when transport proteins for Hb (haptoglobin) are depleted, and free Hb floats around

hemolytic anemia (accelerated red cell turnover)

immune mediated

high

immune hemolytic anemia = marked red cell turnover = increase reticulocyte release = increase MCV due to a big number of polychromatophilic cells released into the blood, which are larger than normal RBC's = increased MCV!

Immune hemolytic anemia!

Hereditary spherocytosis

schistocytes
spherocytes

Autoimmune (warm; cold; paroxysmal cold hemoglobinemia)
Drug induced
Alloimmune - Ab to foreign Ag (hemolytic transfusion rxn; hemolytic dz of the newborn)

IgG @ 37*C

Autoimmune hemolytic anemia (normochromic normocytic)

high incidence Ag's such as the anti-Rh system!

IgM (Ice Cream....MMM)

Lymphoproliferative dz (CLL or Lymphoma/leukemia)! - low-grade B-cell process

the "I" Ag - a high incidence Ag...hard to find compatible blood!

biphasic IgG Ab

Anti-P Ag on RBC's - high incidence Ag ******

Hemolytic Dz of Newborn (Rh incompatibility)

Mother was sensitized with "Anti-D (fetal)" Ab from her last pregnancy..which are now going to attack the 2nd fetus.

Will cause severe anemia & bilirubinemia (kernicterus) in the fetus!!!!*********

Rh incompatibility - only pregnancies after the 1st one affected; Severe anemia & bilirubinemia in fetus....need a transfusion

ABO incompatibility - 1st & subseqient pregnancies may be affected; mild anemia & bilirubinemia...usually jaundice after 48 hrs....use phototherapy as tx!

Drug adsorption - drug binds RBC = acts as a hapten = Ab production for extravascular hemolysis in spleen (mac's bind Fc receptor of bound Ab) ... no compliment activation!
Immune complex - Anti-drug Ab forms an immune complex with the drug in the PLASMA. IC then binds to the drug and activates compliment
Membrane modification/autoAb - drug modifies the membrane of RBC = Ab attacks

coombs test detects Ab AND/OR Complement on RBC's in-vivo

Ab's in patient's SERUM as opposed to RBC's

Enzyme deficiencies*********
Hemoglobinopathies (thalassemia)
Membrane disorders

As glucose is broken down, we generate free ATP as well as free radicals which can oxidize Hb = Hb precipitation = Heinz body formation (anemia) --> G6PD reduces these radicals by reducing NADPH & thus glutathione!

in hemolysis/hemolytic anemia's you always see an INCREASE in reticulocytes...which are young RBC's with increased NADPH = less susceptible to oxidation

can't convert ADP to ATP
RBC potassium leak & membrane deformity
Sequestration in the red pulp of spleen

Hereditary Spherocytosis - deficiency in cytoskeleton spectrin protein = cells lack felxibility = trapped in spleen; cells run out of ATP to pump out Na
Hereditary Elliptocytosis - same as above, but cells are elliptical rather than spherocytes
Paroxysmal Nocturnal Hemoglobinuria - (PNH is acquired...where as the two above are inherited!)

hereditary spherocytosis

acute myelogenous LEUKEMIA

because PNH is an acquired STEM CELL DISORDER...thus can cause leukemia!

intermittent bouts of IVH/nocturnal hemoglobinuruia...possibly due to increased acidosis/hypercapnia at night = complement more active

ALSO..there is deficient regulation of compliment...so can't downgrade compliment = it goes crazy & lyses cells!

PNH is a membrane disorder because there is a membrane deficiency resulting from an absence of an anchoring protein (GPI) on ALL CELL LINES (RBC/WBC/platelets) for CD55/59, which downgrade compliment!

Flow Cytometry to identify the absence of CD55/59 on cell membranes

- but can be insensitive, especially if a pt has had a transfusion, he'll get normal cells with CD55/59 on them = cytometry won't detect anything

Newest flow methods have toxins binding to GPI....so if there is lysis of the cell, you know that GPI is present = NOT PNH...if cells aren't lysing, GPI is absent = PNH!

Microangiopathic Hemolytic Anemia

(direct physical injury, chemicals, drugs are also extrinsic causes of HA, but not as significant!)

SCHISTOCYTES!

HUS is a Childhood dz...usually from eating food infected with a verocytotoxin producing E. coli (VTEC)

hemolytic anemia w/ schistocytes
ARF!
Thrombocytopenia
CNS SYNDROMES! (Seizures)

May also present with Diarrhea!! (Diarrhea +)...if D-negative then most likely a mutation in thrombomodulin

mortality is 90%...so have to catch it!

-Present in YOUNG ADULTS (mainly children in HUS)
-more organ systems damaged in TTP
-neurological sx more severe
-renal dysfunction LESS SEVERE in TTP
-mortality rate HIGHER

Mutation in metalloprotease/ADAMTS13 = can't breakdown vWF = abnormally large vWF multimers

Qualitiative = defect in FORMATION of the Hb molecule (functional defect)

Quantitative = defect in SYNTHESIS of the globin molecule = decrease Hb formation (abnormal amount)

mutations (deletions/substitutions) involving abnormal globin structure formation

genetic defect resulting in reduced production of structurally NORMAL chains (so it's just a reduced # of globin molecules)

variant Hb present

HbF becomes inactive (until then, HbF is protective!)

beta-chain = structurally abnormal globin

AA substitutitions/deletions affect O2 affinity for Hb

High affinity for O2 - decreased O2 delivery to tissue = compensatory erythrocytosis!

Low affinity for O2: premature O2 release into tissue

No affinity for O2: Hb always in reduced state (Fe+3) = HbM = homozygous condition NOT compatible w/ life...so only heterozygous forms are seen!)

Sickle cell anemia/disease

Sickle cell dz

(polar --> nonpolar AA = BAD! - change in net charge can be used to quantify how much HbS is present!)

hypoxia (cells go back to normal shape with reoxygenation!)
acidosis
hypertonicity
temp >37*C

All these states promote DEOXYGENATION = formation of HbS

Sickle Cell Anemia (progressive sickling (from deoxy to oxy) state damages the cells = irreversible sickling = hemolysis)

Hyperplastic bone marrow ...so thick marrow but thin cortex (all due to chronic extravascular hemolysis, which leads to hypercellularity of the BM as a result of compensation for increased red cell turnover)

blockage of microvasculature by rigid sickled cells

Sx: pain, fever, tissue necrosis, infarction of tissues, dactylitis (infarction of metacarpas & metatarsals), thombosis leading to stokes, blindness, ulcers

PNEUMONIA (common) & MENINGITIS (common cause of death!)

CHEST SYNDROME***
- fever, chest pain = due to pulmonary infiltrates from SLUDGING IN THE MICROVASCULATURE!

normochromic normocytic anemia

because 1/4 children can get sickle cell dz (homozygous), while 2/4 will be heterozygous for sickle cell trait

Hemoglobin C

Hemoglobin C (or also C/S)

Hemoglobin C/S = NO HbA formed!

sickling & HbC intracellular crystals

Hemoglobin E

heterozygous (homozygous = death sentence!)

beta thalassema

completely asymptomatic!

NORMAL! it's a hereditary dz (ACD also has normal RDW....but all other anemia's, RDW is elevated)

excess of globin chains from the chain NOT affected results in production of RBC's with abnormal Hb containing an excess of a particular globin chain = unstable Hb = precipitate = Heinz body formation = extravascular removal by the spleen

HOMOzygous Beta Thalassemia MAJOR (Cooley's Anemia)

HETERozygous Beta Thalassemia MINOR - not as severe as beta major since there is still one normal beta gene present...often confused with IDA, but can r/o by doing iron & serum ferratin tests!

erythroid hyperplasia stimulates iron absorption in the gut = iron toxicity (hemochromatosis)

1 deletion - silent carrier
2 deletions - alpha thalassemia trait - mild hypo/micro anemia, target cells, basophilic stippling
3 deletions - HbH dz - moderate hypo/micro anemia, target cells, basophilic stippling, severe hemolytic anemia, HbH (high affinity for O2)
4 deletions - Hydrops Fetalis (fatal!), severe anemia, numerous NRBC's, Hb Barts (gamma4..no alpha's at all = high affinity for O2 = no release of O2 into tissues)

SE Asia!

2,3-DPG COMPETES with O2 for binding sites on Hb

so as 2,3-DPG increases, O2 on Hb decreases (& vice versa)

Bone Marrow HYPOCELLULARITY.....much of the normal marrow is replaced by FAT!

due to depletion, damage, or inhibition of STEM CELL proliferation

ACQUIRED - most common being idiopathic (drugs, rx to chemicals, ciruses, radiation, PNH, neoplasms, etc)

NO...those suggest bone marrow replacement disorders & hypercellularity.....Aplastic Anemia has no bone marrow damage, just hypocellularity and a decrease in stem cell production by the bone marrow!

EPO tries to increase erythropoiesis...but there are no stem cells to do so in aplastic anemia (all 3 germ lines affected)..

thymoma
autoimmune dz's

Myelophtisic Anemia

Myelophthisic Anemia (a bone marrow replacement disorder!)

a bone marrow occupying lesion = leukemia, lymphoma, metastatic carcinoma, sarcoidosis, TB, fibrosis of BM

- NRBC's, polychromasia teardrop cells, aniso/poikilocytosis

BM infiltration by space occupying lesions: tumor, fibrosis, granulomas

leukoerythroblastic reaction/picture = a lot of NRBC's, polychromasia teardrop cells, aniso/poikilocytosis

80-100% BM HYPERcellularity with peripheral cytopenias

Myelophthisic Anemia - space occupying lesion in the BM = BM damage = release of immature cells

myelodysplastic syndrome - clonal pluripotential stem cell disorder (refractory anemia!) where there is 80-100% hypercellularity in the bone marrow, but peripheral cytopenia with anemia! >20% blast cells then progresses to LEUKEMIA!

vascular constriction (always 1st!)
platelet aggregation - 1* hemostasis
fibrin formation 2* hemostasis (with almost simultaneous fibrinolysis starting)

thrombogenic - vWF

anti-thrombogenic - thrombomodulin

found in vascular endothelium, it activates Protein C...which goes on to inhibit Factor 5a & 8a

Dense Bodies - mediators of plt function:
ADP
ATP
Ca****
serotonin

Alpha Granules - pro-coag function: Factor 5
fibrinogen
vWF
plasminogen (fibrinolysis)
PAI-1 (inhibits plasminogen)

platelet:
adhesion - GPIb receptors on platelet bind vWF
activation - exposure of GPIIb/IIIa receptors on platelets
aggregation - fibrinogen & calcium work together to bind platelets together
secretion - platelets release GRANULE contents (ADP, Ca),etc, which exposes more GPIIb/IIIa receptors

and thus...the priamary heomstatic plug is formed

make an incision on the forum and time how long it takes bleeding to stop with a stopwatch

done to measure primary hemostasis!

Platelet Function Analyzer

Closure Time (a high CT = platelet dysfunction)

inherited platelet defect
acquired drug related disorder

Normal after collagen&ADP = drug reaction
Abnormal after collagen&ADP = inherited platelet defect

mainly activating fibrinolysis! & serve as inflammatory mediators

F12 & kallikrein convert PLASMINOGEN to PLASMIN

Bradykinin = clot breakdown!

Other than converting fibrinogen to fibrin, thrombin activates:
Factor 5
Factor 8
Factor 11
Factor 13 - helps in fibrin cross-linking (hard clot)
Protein C/S by binding thrombomodulin - goes on to inhibitor thrombin...so self-regulation!

Factors 2, 7, 9, 10

Require Vit K, Ca, & Phospholipid!!!

to provide the critical Calcium receptors necessary for binding the pro-coagulant factors (factors 2, 7, 9, 10) to phospholipid!

Factors still synthesized in the liver, & released into the plasma, but nonfunctional

plasma = contains all coagulation factors
Serum = plasma w/o clotting factors

secondary hemostasis (coagulation) - fibrin formation

used during surgery when a person is on a pump to make sure the person is adequately anticoagulated

only conversion of fibrinogen to fibrin

common pathway

it monitors the PRESENCE of heparin (not therapy...but just whether it in the body or not!)

plasmin

both fibrinogen & fibrinm, (but pretty much all serine proteases factors...which are all factors except factor 13!)

tPA - tissue plasminogen activator..released from endothelium

but there are many others: streptokinase (drug), urokinase, factor 12, kallikrein

Fibrin Degradation Product Assay - uses a monoclonal Ab specific to the break down product

D-dimer - it's specific only F13 cross-linked fibrin (hard clot) = tells you that the coagulation cascade has been activated (since F13 was working) = so an excellent marker for cascade activation!!!

****** Heparin binds to antithrombin, causing a conformational change, enhancing the rate of thrombin/Antithrombin complex by a factor of 1000!!!!!

inhibits Factor 5a, 8a & PAI-1 (it's a Vit K dependent factor!)

Thrombin binds thrombomodulin on the endothelium, and with Ca, it activates protein C

helps bind Protein C to phospholipid surface of platelets (due to it's high affinity for phospholipids) and to endothelium...increasing inactivation of Factor 5a & 8a

platelet or vessel = mainly 1* hemostasis

platelet, vessel or coagulation factors = 1* OR 2* hemostasis

Kids (2-6yo); IgG Ab against platelets; outcome is good = spontaneous remission

young women (20-40yo); Ab against GPIIb/IIIa; Spleen is the site of Ab production & destruction...so if reoccurs..need a splenectomy!

DAT test should be positive!!!

YES...Ab (IgG!) can cross the placenta and attack the fetus's platelets

Type I = non-immune = direct effect of heparin on platelet activation = platelet count decreases to >50,000

first few days of drug

Often asymptomatic; Spontaneous recovery of platelet count EVEN IF heparin is continued

Type II = Immune mediated = HITS SYNDROME!!!

Ab to Heparin-PF4 complex = Fc affixing to platelet surface resulting in platelet activation = increases thrombosis but ineffective

SEVERE DROP in platelet count (<50k) with thrombosis (SKIN GANGRENE, MI, STROKE!)

Occurs 5-15 days if new heparin user, but hours to days if previous heparin user

Prognosis = platelet count recovers only after heparin is discontinued

Primary - symptomatic - platelet count >1 million

Secondary - asymptomatic - platelet count <1 million

platelet satellitism - platelets surrounds neutrophils due to Ab activation

B-Sad! (Bernard-Soulier = adhesion!)

adhesion of platelets to the endothelial membrane

due to decreased/abnormal GPIb on platelet surface

This is a QUALTATIVE (functional) platelet defect (normal platelet count & morphology)

Glanzmann = platelet aGgregation

due to absent GPIIb/IIIa on platelet surfaces

This is a QUALTATIVE (functional) platelet defect (normal platelet count & morphology)

deficiency in ALPHA granules = since they are so numerous = Gray Platelet Syndrome!

8

So in vWB Dz...absence of vWF = decrease activity of Factor 8 = bleeding

Its variability = sx may begin at birth or second decade of life...with no correlation to levels of vWF!

Platelet Count = normal
Bleeding Time = elevated
PT = normal
aPTT = normal or elevated (due to Factor 8 deficiency)

8 = no amplification of the intrinsic pathway = increase aPTT

(remember...it's X-linked...so only MALES affected!)

9 = no amplification of the intrinsic pathway = increase aPTT

(remember...it's X-linked...so only MALES affected!)

Hemophilia A/B!

initial bleeding was stopped due to platelets binding (1* hemostasis not affected)

second bleed due to absence of secondary pathway (bleeding into joints = hemarthrosis)

Factor Activity Level - the more of factor 8/9 present, the better the outcome (don't need much!!!)

pt's treated with FACTOR CONCENTRATES may develop an allo/auto-Ab to Factor 8/9 = severe bleeding

Tx by giving EXCESS Factor 8/9 to overwhelm the inhibitor!

Recombinant Factor 7a = initiatie the extrinsic cascade to kick off the common pathway...but NO AMPLIFICATION

DIC

fibrin degradation products (FDP) = so increased clotting (platelets used up), but the clots are being broken down quickly = increased FDP

hemorrhagic bleeding, which starts abruptly from at least 3 sites

a lot of thrombosis (more than bleeding) = infarcts;

D-dimer = positive = pt is clotting
platelet = decreased count
fibrinogen = decreased
PT = increased
aPTT = increased
TT = incrased

procoagulation factors ARE NOT produced (usually made in the liver) = bleeding

nonfunctional calcium binding sites = Factors 2, 7, 9, 10, Protein C & S do NOT bind the endothelium!

it's a lab phenomonenon = not associated with bleeding!

Ab reacts with phospholipid surfaces, which are used for the test reagents = prolonging the test results!

may demonstrate thrombosis (placental abortions!)

Systemic lupus er.

Anticardiolipin (ACA) = does same thing as lupus....binds phospholipd membrane where the test reagents bind = prolong the test result

Warfarin

fractioned (low-molecular weight) heparin

Incrase the effect of AT on Factor 10a inhibition

Production of mutant Factor V that cannot be degraded by protein C

mutation in prothrombin increases the effect and conversion of prothrombin to thrombin = hypercoagulable!

Antiphospholipid Antibody Syndrome = syphilis is a FALSE positive!

hypercoagulation = arterial thrombosisi
skeletal & occular defects
mental retardation

TRALI = Transfussion Related Acute Lung Injury

Granulocyte/HLA Ab IN THE DONOR**** that react with the patients WHITE cells = white cells aggregate in the lungs to mimic ARDS & pulmonary edema!